Variant 9-137169135-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The ENST00000371542.3(LRRC26):c.724C>G(p.Leu242Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00129 in 1,555,936 control chromosomes in the GnomAD database, including 30 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0070 ( 14 hom., cov: 33)

Exomes 𝑓: 0.00067 ( 16 hom. )

Consequence

LRRC26
ENST00000371542.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.579

Variant links:

Genes affected

LRRC26 (HGNC:31409): (leucine rich repeat containing 26) Enables potassium channel activator activity; transmembrane transporter binding activity; and voltage-gated potassium channel activity. Involved in positive regulation of voltage-gated potassium channel activity and potassium ion transmembrane transport. Is integral component of plasma membrane. Part of voltage-gated potassium channel complex. [provided by Alliance of Genome Resources, Apr 2022]

LRRC26 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0028005242).

BP6

Variant 9-137169135-G-C is Benign according to our data. Variant chr9-137169135-G-C is described in ClinVar as [Benign]. Clinvar id is 776483.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00699 (1063/152128) while in subpopulation AFR AF= 0.0244 (1015/41550). AF 95% confidence interval is 0.0232. There are 14 homozygotes in gnomad4. There are 508 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1063 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRRC26	NM_001013653.3 linkuse as main transcript	c.724C>G	p.Leu242Val	missense_variant	2/2	ENST00000371542.3	NP_001013675.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRRC26	ENST00000371542.3 linkuse as main transcript	c.724C>G	p.Leu242Val	missense_variant	2/2	1	NM_001013653.3	ENSP00000360597	P1	Q2I0M4-1

Frequencies

GnomAD3 genomes

AF:

0.00696

AC:

1058

AN:

152020

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0244

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00183

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00766

GnomAD3 exomes

AF:

0.00144

AC:

262

AN:

182194

Hom.:

AF XY:

0.00113

AC XY:

116

AN XY:

102772

show subpopulations

Gnomad AFR exome

AF:

0.0237

Gnomad AMR exome

AF:

0.00150

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000815

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000358

Gnomad OTH exome

AF:

0.000234

GnomAD4 exome

AF:

0.000670

AC:

941

AN:

1403808

Hom.:

Cov.:

AF XY:

0.000611

AC XY:

426

AN XY:

697508

show subpopulations

Gnomad4 AFR exome

AF:

0.0264

Gnomad4 AMR exome

AF:

0.00158

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000497

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000128

Gnomad4 OTH exome

AF:

0.00143

GnomAD4 genome

AF:

0.00699

AC:

1063

AN:

152128

Hom.:

Cov.:

AF XY:

0.00683

AC XY:

508

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.0244

Gnomad4 AMR

AF:

0.00183

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00758

Alfa

AF:

0.00331

Hom.:

Bravo

AF:

0.00798

ESP6500AA

AF:

0.0152

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00197

AC:

235

Asia WGS

AF:

0.000874

AC:

AN:

3448

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 13, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.0083

Eigen

Benign

-0.56

Eigen_PC

Benign

-0.67

FATHMM_MKL

Benign

0.046

LIST_S2

Benign

0.45

MetaRNN

Benign

0.0028

MetaSVM

Benign

-0.97

MutationAssessor

Uncertain

2.3

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.62

PROVEAN

Benign

-1.1

REVEL

Benign

0.076

Sift

Benign

0.058

Sift4G

Benign

0.30

Polyphen

0.61

Vest4

0.13

MVP

0.27

MPC

0.79

ClinPred

0.0067

GERP RS

0.17

Varity_R

0.076

gMVP

0.33

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over